The blood brain barrier (BBB) limits the application of most therapeutic drugs for neurological diseases (NDs). Hybrid cell membrane‐coated nanoparticles derived from different cell types can mimic ...the surface properties and functionalities of the source cells, further enhancing their targeting precision and therapeutic efficacy. Neuroinflammation has been increasingly recognized as a critical factor in the pathogenesis of various NDs, especially Alzheimer's disease (AD). In this study, a novel cell membrane coating is designed by hybridizing the membrane from platelets and chemokine (C–C motif) receptor 2 (CCR2) cells are overexpressed to cross the BBB and target neuroinflammatory lesions. Past unsuccessful endeavors in AD drug development underscore the challenge of achieving favorable outcomes when utilizing single‐mechanism drugs.Two drugs with different mechanisms of actions into liposomes are successfully loaded to realize multitargeting treatment. In a transgenic mouse model for familial AD (5xFAD), the administration of these drug‐loaded hybrid cell membrane liposomes results in a significant reduction in amyloid plaque deposition, neuroinflammation, and cognitive impairments. Collectively, the hybrid cell membrane‐coated nanomaterials offer new opportunities for precise drug delivery and disease‐specific targeting, which represent a versatile platform for targeted therapy in AD.
A novel cell membrane coating is designed by hybridizing the membranes from platelets and chemokine receptor 2 overexpressing cells to cross the blood brain barrier (BBB) and target neuroinflammatory lesions. Rapamycin and 1‐trifluoromethoxyphenyl‐3‐(1‐propionylpiperidin‐4‐yl) urea (TPPU) are loaded into the liposomes to achieve a synergistic therapy. These drug‐loaded hybrid cell membrane‐coated liposomes precisely target specific lesions and ameliorate cognitive deficiency in Alzheimer's disease.
Efficient Core Maintenance in Large Dynamic Graphs Rong-Hua Li; Yu, Jeffrey Xu; Rui Mao
IEEE transactions on knowledge and data engineering,
2014-Oct., 2014-10-00, 20141001, Letnik:
26, Številka:
10
Journal Article
Recenzirano
Odprti dostop
The k-core decomposition in a graph is a fundamental problem for social network analysis. The problem of k-core decomposition is to calculate the core number for every node in a graph. Previous ...studies mainly focus on k-core decomposition in a static graph. There exists a linear time algorithm for k-core decomposition in a static graph. However, in many real-world applications such as online social networks and the Internet, the graph typically evolves overtime. In such applications, a key issue is to maintain the core numbers of nodes when the graph changes overtime. A simple implementation is to perform the linear time algorithm to recompute the core number for every node after the graph is updated. Such simple implementation is expensive when the graph is very large. In this paper, we propose a new efficient algorithm to maintain the core number for every node in a dynamic graph. Our main result is that only certain nodes need to update their core numbers when the graph is changed by inserting/deleting an edge. We devise an efficient algorithm to identify and recompute the core numbers of such nodes. The complexity of our algorithm is independent of the graph size. In addition, to further accelerate the algorithm, we develop two pruning strategies by exploiting the lower and upper bounds of the core number. Finally, we conduct extensive experiments over both real-world and synthetic datasets, and the results demonstrate the efficiency of the proposed algorithm.
C1q and tumour necrosis factor-related protein 1 (CTRP1) possesses anti-atherogenic and anti-inflammatory effects. This study investigated whether the CTRP1 levels in the plasma and epicardial ...adipose tissue (EAT) were associated with congestive heart failure (CHF) and to disclose possible molecular mechanisms.
Plasma and tissue samples were obtained from subjects with or without CHF. Plasma levels of CTRP1 were measured by ELISA. The mRNA levels of CTRP1 and inflammatory cytokines were detected by RT-PCR. The protein levels of CTRP1, aldosterone synthase (CYP11B2) and mitogen-activated protein kinase were examined by Western blotting.
The levels of CTRP1 in the plasma and EAT were higher in the CHF patients than those in the controls. There were no differences in the CTRP1 levels in cardiomyocytes between the CHF group and the non-CHF group. An exploratory survival analysis showed that higher CTRP1 values at admission were associated with a worse prognosis after discharge. CTRP1 increased the IL-6 mRNA level in H295R cells. CTRP1 recruited ERK1/2 and Jak-2 for aldosterone release by modulating the CYP11B2 protein level, and brain natriuretic peptide repressed the CTRP1-induced aldosterone release through the JAK2-STAT3 signalling pathways.
The CTRP1 levels in the plasma and EAT were increased in the CHF patients. CTRP1 is involved in the pathogenesis of CHF by modulating IL-6 levels and aldosterone release.
Objectives
To determine and validate alanine aminotransferase (ALT)-adapted dual cut-offs of liver stiffness measurements (LSMs) for assessing liver fibrosis with two-dimensional shear wave ...elastography (2D-SWE) in patients with chronic hepatitis B (CHB) infection.
Methods
Patients with CHB infection who underwent liver biopsy to assess liver fibrosis were consecutively included. 2D-SWE confirmation thresholds with a positive likelihood ratio ≥10 and 2D-SWE exclusion thresholds with a negative likelihood ratio ≤0.1 were identified to rule in or rule out significant fibrosis and cirrhosis, respectively.
Results
The first 515 patients (index cohort) and the next 421 patients (validation cohort) were included in the final analysis. The low and high cut-offs to rule out and rule in patients with significant fibrosis (≥ F2) were 5.4 kPa and 9.0 kPa, respectively, in patients with ALT levels ≤ 2 × the upper limit of normal (ULN) and 7.1 kPa and 11.2 kPa in patients with ALT levels > 2 × ULN. For cirrhosis (F4), the corresponding values were 8.1 kPa and 12.3 kPa in patients with ALT levels ≤ 2 × ULN and 11.9 kPa and 24.7 kPa in patients with ALT levels > 2 × ULN. The dual cut-off values showed an overall accuracy of more than 90% for diagnosis of the presence or absence of significant fibrosis and cirrhosis in the index and validation cohorts. There were no significant differences in the accuracy values between the cohorts (all
p
>0.05).
Conclusion
The ALT-adapted dual cut-offs of LSMs showed high accuracy for diagnosis of the presence or absence of significant fibrosis and cirrhosis in patients with CHB infection.
Key Points
• The ALT-adapted dual cut-off values of LSMs showed high accuracy for diagnosis of the presence or absence of significant fibrosis and cirrhosis.
• ALT levels did not influence the overall diagnostic accuracy for predicting significant fibrosis and cirrhosis.
• The ALT-adapted dual cut-offs in patients with ALT levels > 2 × ULN were markedly higher than those in patients with ALT levels
≤
2 × ULN.
Peptide-based materials that have diverse structures and functionalities are an important type of biomaterials. In former times, peptide-based nanomaterials with excellent stability were constructed ...through self-assembly. Compared with individual peptides, peptide-based self-assembly nanomaterials that form well-ordered superstructures possess many advantages such as good thermo- and mechanical stability, semiconductivity, piezoelectricity and optical properties. Moreover, due to their excellent biocompatibility and biological activity, peptide-based self-assembly nanomaterials have been vastly used in different fields. In this review, we provide the advances of peptide-based self-assembly nanostructures, focusing on the driving forces that dominate peptide self-assembly and assembly mechanisms of peptides. After that, we outline the synthesis and properties of peptide-based nanomaterials, followed by the applications of functional peptide nanomaterials. Finally, we provide perspectives on the challenges and future of peptide-based nanomaterials.
Peptide-based self-assembly nanomaterials possess many advantages. Based on their ability to self-assemble, peptide nanomaterials provide huge potential applications in biomedical and material technologies. The widespread applications of peptide nanomaterials can significantly affect our daily life in the future. Display omitted
•This review summarizes the advances of peptide-based nanomaterials, focusing on the mechanisms, properties, and applications.•Outlining the synthesis and properties of peptide nanomaterials is helpful for the relevant research fields.•The peptide-based nanomaterials show potential applications in many fields.
Early detection and accurate monitoring of chronic kidney disease (CKD) could improve care and retard progression to end-stage renal disease. Here, using untargeted metabolomics in 2155 participants ...including patients with stage 1-5 CKD and healthy controls, we identify five metabolites, including 5-methoxytryptophan (5-MTP), whose levels strongly correlate with clinical markers of kidney disease. 5-MTP levels decrease with progression of CKD, and in mouse kidneys after unilateral ureteral obstruction (UUO). Treatment with 5-MTP ameliorates renal interstitial fibrosis, inhibits IκB/NF-κB signaling, and enhances Keap1/Nrf2 signaling in mice with UUO or ischemia/reperfusion injury, as well as in cultured human kidney cells. Overexpression of tryptophan hydroxylase-1 (TPH-1), an enzyme involved in 5-MTP synthesis, reduces renal injury by attenuating renal inflammation and fibrosis, whereas TPH-1 deficiency exacerbates renal injury and fibrosis by activating NF-κB and inhibiting Nrf2 pathways. Together, our results suggest that TPH-1 may serve as a target in the treatment of CKD.
A novel printed log-periodic dipole array (PLPDA) antenna with bow-tie parasitic cell for the gain enhancement is presented for 5G mobile and wireless communication. The antenna is fed by the ...substrate integrated waveguide. The gain of the antenna is enhanced using parasitic cell-several bow-tie directors and bow-tie parasitic patches. The adding of bow-tie directors are based on the principle of the quasi-Yagi and the bow-tie antenna. Moreover, the parasitic patches are used to enhance the antenna gain by expanding the transverse radiation aperture of the antenna according to the principle of the antenna array. The proposed antenna has been designed, fabricated, and tested. It can be observed that the PLPDA antenna gain with the parasitic cell is increased about 1-dBi compared with the antenna with the single-sided rectangle directors. And the S11 of the proposed antenna is less than -12 dB, the cross-polarization level is better than -15 dB, and the gain of the presented antenna is 7.3-12.5 dBi over the whole operating frequency range of 40-50 GHz.
Photocatalytic reduction of CO2 to value-added fuels is a promising route to reduce global warming and enhance energy supply. However, poor selectivity and low efficiency of catalysts are usually the ...limiting factor of their applicability. Herein, a photoinduction method was developed to achieve the formation of Cu single atoms on a UiO-66-NH2 support (Cu SAs/UiO-66-NH2) that could significantly boost the photoreduction of CO2 to liquid fuels. Notably, the developed Cu SAs/UiO-66-NH2 achieved the solar-driven conversion of CO2 to methanol and ethanol with an evolution rate of 5.33 and 4.22 μmol h–1 g–1, respectively. These yields were much higher than those of pristine UiO-66-NH2 and Cu nanoparticles/UiO-66-NH2 composites. Theoretical calculations revealed that the introduction of the Cu SAs on the UiO-66-NH2 greatly facilitates the conversion of CO2 to CHO* and CO* intermediates, leading to excellent selectivity toward methanol and ethanol. This study provides new insights for designing high-performance catalyst for photocatalytic reduction of CO2 at the atomic scale.
A falling-head test is a common method to estimate aquifer properties in which the water level in a well is increased suddenly, which is a key assumption for the data to be analyzed by traditional ...methods such as Cooper et al. and Hvorslev methods. However, there are situations where the water level increases in the well occurs for a relatively long period before it falls. In this case theoretically, there is no existing method to analyze the data. Hydrogeologists or geotechnical engineers still use the traditional methods to analyze the data even the water level increase is not instantaneous. This study derives a semi-analytical solution to describe water level change in this case. The mathematical model consists of the injection stage and water level fall stage. It is found that the water level mound induced by non-instantaneous injection leads to slower decrease of water level in the well comparing to the instantaneous injection. This study further analyses the errors of the estimated hydraulic properties if the data are analyzed by traditional methods. If calculated by Cooper et al. method, the storativity is underestimated but there is no impact on estimated hydraulic conductivity. The hydraulic conductivity calculated by Hvorslev method is underestimated and the error of underestimation increases with injection time and aquifer parameters. The actual hydraulic conductivity can be a few times of the estimated value for typical aquifer parameters in Hong Kong. Furthermore, a field experiment is conducted to compare the instantaneous method, non-instantaneous method and field data. The present solution fits the data well, and the errors of estimated parameters by instantaneous injection method are consistent with the conclusions in the error analysis.
•Analytical solution to the falling-head test with non-instantaneous injection.•Water level mound induced by non-instantaneous injection causes the slower fall.•Storativity and hydraulic conductivity are underestimated by instantaneous method.•The proposed solution matches the field data well.•Errors of parameters estimated by field data are consistent with error analysis.
Wilms tumor gene on the X chromosome (WTX) is a putative tumor suppressor gene in Wilms tumor, but its expression and functions in other tumors are unclear. Colorectal cancer (CRC) is the third ...leading cause of cancer-related deaths in women and the second leading cause in men in the United States. We demonstrated that WTX frequently lost in CRC which was highly correlated with cell proliferation, tumor invasion and metastasis. Mechanistically, WTX loss disrupts the interaction between RhoGDIα and CDC42 by losing of the binding with RhoGDIα and triggers the activation of CDC42 and its downstream cascades, which promotes CRC development and liver metastasis. The aberrant upregulation of miR-20a/miR-106a were identified as the reason of WTX loss in CRC both in vivo and in vitro. These study defined the mechanism how miR-20a/miR-106a-mediated WTX loss regulates CRC progression and metastasis, and provided a potential therapeutic target for preventing CRC progression.
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